Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Orlando Immunology Center, Orlando, FL, USA.
Lancet. 2012 Jun 30;379(9835):2439-2448. doi: 10.1016/S0140-6736(12)60917-9.
The integrase inhibitor elvitegravir (EVG) has been co-formulated with the CYP3A4 inhibitor cobicistat (COBI), emtricitabine (FTC), and tenofovir disoproxil fumarate (TDF) in a single tablet given once daily. We compared the efficacy and safety of EVG/COBI/FTC/TDF with standard of care-co-formulated efavirenz (EFV)/FTC/TDF-as initial treatment for HIV infection.
In this phase 3 trial, treatment-naive patients from outpatient clinics in North America were randomly assigned by computer-generated allocation sequence with a block size of four in a 1:1 ratio to receive EVG/COBI/FTC/TDF or EFV/FTC/TDF, once daily, plus matching placebo. Patients and study staff involved in giving study treatment, assessing outcomes, and collecting and analysing data were masked to treatment allocation. Eligibility criteria included screening HIV RNA concentration of 5000 copies per mL or more, and susceptibility to efavirenz, emtricitabine, and tenofovir. The primary endpoint was HIV RNA concentration of fewer than 50 copies per mL at week 48. The study is registered with ClinicalTrials.gov, number NCT01095796.
700 patients were randomly assigned and treated (348 with EVG/COBI/FTC/TDF, 352 with EFV/FTC/TDF). EVG/COBI/FTC/TDF was non-inferior to EFV/FTC/TDF; 305/348 (87·6%) versus 296/352 (84·1%) of patients had HIV RNA concentrations of fewer than 50 copies per mL at week 48 (difference 3·6%, 95% CI -1·6% to 8·8%). Proportions of patients discontinuing drugs for adverse events did not differ substantially (13/348 in the EVG/COBI/FTC/TDF group vs 18/352 in the EFV/FTC/TDF group). Nausea was more common with EVG/COBI/FTC/TDF than with EFV/FTC/TDF (72/348 vs 48/352) and dizziness (23/348 vs 86/352), abnormal dreams (53/348 vs 95/352), insomnia (30/348 vs 49/352), and rash (22/348 vs 43/352) were less common. Serum creatinine concentration increased more by week 48 in the EVG/COBI/FTC/TDF group than in the EFV/FTC/TDF group (median 13 μmol/L, IQR 5 to 20 vs 1 μmol/L, -6 to 8; p<0·001).
If regulatory approval is given, EVG/COBI/FTC/TDF would be the only single-tablet, once-daily, integrase-inhibitor-based regimen for initial treatment of HIV infection.
Gilead Sciences.
整合酶抑制剂艾维雷韦（EVG）与 CYP3A4 抑制剂考比司他（COBI）、恩曲他滨（FTC）和富马酸替诺福韦二吡呋酯（TDF）联合制成复方片剂，每日一次给药。我们比较了艾维雷韦/考比司他/恩曲他滨/富马酸替诺福韦二吡呋酯（EVG/COBI/FTC/TDF）与标准治疗方案依非韦伦（EFV）/FTC/TDF 作为初始治疗 HIV 感染的疗效和安全性。
在这项 3 期临床试验中，来自北美的门诊诊所的初治患者通过计算机生成的分配序列，以 4 个为一组的块大小随机分配，1:1 比例接受 EVG/COBI/FTC/TDF 或 EFV/FTC/TDF，每日一次，同时给予匹配的安慰剂。参与治疗、评估结局、收集和分析数据的患者和研究人员对治疗分配进行了盲法。入选标准包括筛选时 HIV RNA 浓度为 5000 拷贝/ml 或以上，对依非韦伦、恩曲他滨和替诺福韦敏感。主要终点为第 48 周时 HIV RNA 浓度小于 50 拷贝/ml。该研究在 ClinicalTrials.gov 注册，编号为 NCT01095796。
700 名患者被随机分配并接受治疗（EVG/COBI/FTC/TDF 组 348 名，EFV/FTC/TDF 组 352 名）。EVG/COBI/FTC/TDF 不劣于 EFV/FTC/TDF；第 48 周时，305/348（87.6%）名患者的 HIV RNA 浓度小于 50 拷贝/ml，而 296/352（84.1%）名患者达到这一标准（差异为 3.6%，95%CI -1.6%至 8.8%）。因不良反应停药的患者比例差异不大（EVG/COBI/FTC/TDF 组 13/348 例 vs EFV/FTC/TDF 组 18/352 例）。与 EFV/FTC/TDF 相比，EVG/COBI/FTC/TDF 更常见恶心（72/348 例 vs 48/352 例）和头晕（23/348 例 vs 86/352 例），少见异常梦境（53/348 例 vs 95/352 例）、失眠（30/348 例 vs 49/352 例）和皮疹（22/348 例 vs 43/352 例）。EVG/COBI/FTC/TDF 组第 48 周时血清肌酐浓度升高较 EFV/FTC/TDF 组更为显著（中位数 13 μmol/L，IQR 5 至 20 比 1 μmol/L，-6 至 8；p<0.001）。
如果获得监管部门批准，艾维雷韦/考比司他/恩曲他滨/富马酸替诺福韦二吡呋酯将成为唯一一种用于初始治疗 HIV 感染的每日一次、整合酶抑制剂为基础的单片复方制剂。
吉利德科学公司。
